Spermine Does Not Compete with Omega-conotoxin GVIA in the Striatum Radiatum of the Hippocampal Slice

The effect of spermine (Spm) and of omega-conotoxin GVIA (CTX) on the population excitatory postsynaptic potentials (pEPSP) in stratum radiatum of the CA1 area were compared. CTX decreased irreversibly the initial slope of pEPSP by 57%. Spm produced a maximum inhibition of 85% with an apparent dissociation constant of 0.85 mM and a maximum Hill coefficient larger than 3. The effect of Spm was mostly reversible. Preincubation with Spm did not protect the slice from the irreversible effect of CTX suggesting that they interact with different sites. Since CTX and Spm inhibited pEPSPs with very different affinities and reversibilities a kinetic model was developed to compare their effects. This model relates the inhibitors' binding to presynaptic voltage-activated Ca2+ channels (VACC) with inhibition of pEPSP. The model suggest that: all CTX and Spm effects can be explained by inhibition of VACC. Spm and CTX do not compete for the same site. CTX inhibits 20% (N-type) and Spm 40% of channels (probably the Q-type). More than three Spm molecules bind per one channel molecule, while one CTX is sufficient to inhibit channel function. The model also illustrates that the inhibitor concentration-pEPSP inhibition curves display a Hill coefficient similar to that for inhibitor binding.